During the past two years a study was conducted in our laboratory and during two consecutive summers in Bangkok concerned with the elucidation of the pathogenetic mechanisms underlying the hemorrhagic shock syndrome in dengue hemorrhagic fever, (DHF). The study revealed that complement consumption was greatly increased during shock and that there existed a good correlation between the degree of complement consumption and severity of illness. The proposed project is an extension of that work and concerns itself with the events leading to the initiation of complement activation on the one hand, and the pathogenetic role of platelets and anaphylatoxins on the other hand. It can be divided into four parts: a. First, attempts will be made to detect virus-antibody complexes or Clq reactive material in serum samples of Dengue patients. b. Secondly, in order to establish an in vitro model for Dengue virus replication and expression of viral antigen, human peripheral lymphocytes and human lymphoblastoid cell lines will be infected with the Dengue virus. Replication of the virus in these cell cultures will be measured. Virus-antibody complexes, formed after addition of human antibody, on cell surfaces or in the culture medium will be characterized. C. Thirdly, the effect of virus alone and in the presence of antibody and complement on thrombocytes and rat mast cells will be studied with regard to release of vasoactive amines, and generation of platelet procoagulant activity. d. Fourthly, the role of anaphylatoxins, split products of the complement proteins C3 and C5, of the serum anaphylatoxin inactivator (Al), serum enzyme inhibitors, and of vasoactive amines during shock will be investigated.